ES2461615T3 - Promotores de la apoptosis que contienen N-acilsulfonamida - Google Patents
Promotores de la apoptosis que contienen N-acilsulfonamida Download PDFInfo
- Publication number
- ES2461615T3 ES2461615T3 ES10178948.5T ES10178948T ES2461615T3 ES 2461615 T3 ES2461615 T3 ES 2461615T3 ES 10178948 T ES10178948 T ES 10178948T ES 2461615 T3 ES2461615 T3 ES 2461615T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- phenylsulfanyl
- piperazin
- amino
- propylamino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 230000006907 apoptotic process Effects 0.000 title description 4
- -1 tetrahydrofuranoyl Chemical group 0.000 claims abstract description 2223
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 103
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 99
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 94
- 150000001875 compounds Chemical class 0.000 claims abstract description 85
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 81
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 40
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 37
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 26
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 23
- 125000001424 substituent group Chemical group 0.000 claims abstract description 22
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910003204 NH2 Inorganic materials 0.000 claims abstract description 19
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 19
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 18
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 15
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 13
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 13
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims abstract description 9
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 9
- 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 8
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 8
- 125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 7
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims abstract description 6
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract description 6
- 150000003852 triazoles Chemical class 0.000 claims abstract description 6
- 125000002541 furyl group Chemical group 0.000 claims abstract description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 5
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 5
- 101150009274 nhr-1 gene Proteins 0.000 claims abstract description 5
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims abstract description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims abstract description 4
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims abstract description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 4
- RXBMEHOLQJITJI-LEOXJPRUSA-N (4s)-5-amino-4-[[(2s)-2-[[(2s)-2-[[(4-bromophenyl)-hydroxyphosphoryl]methyl]-3-(3-phenyl-1,2-oxazol-5-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoic acid Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N)CP(O)(=O)C=1C=CC(Br)=CC=1)C(ON=1)=CC=1C1=CC=CC=C1 RXBMEHOLQJITJI-LEOXJPRUSA-N 0.000 claims abstract description 3
- 125000000355 1,3-benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims abstract description 3
- NCTHHJRIJGFPTG-UHFFFAOYSA-N 6,7-bis(aziridin-1-yl)-4-[7-[[6,7-bis(aziridin-1-yl)-5,8-dioxoquinazolin-4-yl]amino]heptylamino]quinazoline-5,8-dione Chemical compound C1CN1C=1C(=O)C2=C(NCCCCCCCNC=3C=4C(=O)C(N5CC5)=C(N5CC5)C(=O)C=4N=CN=3)N=CN=C2C(=O)C=1N1CC1 NCTHHJRIJGFPTG-UHFFFAOYSA-N 0.000 claims abstract description 3
- 101100294108 Caenorhabditis elegans nhr-41 gene Proteins 0.000 claims abstract description 3
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- 125000002393 azetidinyl group Chemical group 0.000 claims abstract description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 3
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 3
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 claims abstract description 3
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 claims abstract description 3
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims abstract description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 3
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims abstract description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims abstract description 3
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims abstract 2
- 238000011282 treatment Methods 0.000 claims description 14
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- 238000000034 method Methods 0.000 claims description 7
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- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 6
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- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 4
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 4
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 4
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 4
- 229960004316 cisplatin Drugs 0.000 claims description 4
- 229960004679 doxorubicin Drugs 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 4
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 4
- 229960004528 vincristine Drugs 0.000 claims description 4
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 4
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- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 3
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- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 3
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 356
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 291
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 262
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- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 169
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 106
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 106
- 239000012141 concentrate Substances 0.000 description 99
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 92
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 89
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 85
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- 238000005481 NMR spectroscopy Methods 0.000 description 59
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 59
- 239000000284 extract Substances 0.000 description 56
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- QGDBAWRHDYBDOG-PSXMRANNSA-N n-[4-[[(2r)-4-imidazol-1-yl-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonyl-4-[4-[(2-phenylphenyl)methyl]piperazin-1-yl]benzamide Chemical compound C([C@@H](NC1=CC=C(C=C1[N+](=O)[O-])S(=O)(=O)NC(=O)C=1C=CC(=CC=1)N1CCN(CC=2C(=CC=CC=2)C=2C=CC=CC=2)CC1)CSC=1C=CC=CC=1)CN1C=CN=C1 QGDBAWRHDYBDOG-PSXMRANNSA-N 0.000 description 1
- KCRNCEURXRNMEG-PSXMRANNSA-N n-[4-[[(2r)-5-methyl-1-phenylsulfanylhexan-2-yl]amino]-3-nitrophenyl]sulfonyl-4-[4-[(2-phenylphenyl)methyl]piperazin-1-yl]benzamide Chemical compound C([C@@H](CCC(C)C)NC=1C(=CC(=CC=1)S(=O)(=O)NC(=O)C=1C=CC(=CC=1)N1CCN(CC=2C(=CC=CC=2)C=2C=CC=CC=2)CC1)[N+]([O-])=O)SC1=CC=CC=C1 KCRNCEURXRNMEG-PSXMRANNSA-N 0.000 description 1
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- ADTHIDLKHDPOKG-UHFFFAOYSA-N n-[4-[[1-(benzenesulfonyl)-2-methylpropan-2-yl]amino]-3-nitrophenyl]sulfonyl-4-[4-[[2-(4-chlorophenyl)phenyl]methyl]piperazin-1-yl]benzamide Chemical compound C=1C=C(S(=O)(=O)NC(=O)C=2C=CC(=CC=2)N2CCN(CC=3C(=CC=CC=3)C=3C=CC(Cl)=CC=3)CC2)C=C([N+]([O-])=O)C=1NC(C)(C)CS(=O)(=O)C1=CC=CC=C1 ADTHIDLKHDPOKG-UHFFFAOYSA-N 0.000 description 1
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- URAOSMGQEFPAGH-PMERELPUSA-N n-[4-[methyl-[methyl-[(1s)-1-phenylethyl]carbamoyl]amino]-3-nitrophenyl]sulfonyl-4-[4-[(2-phenylphenyl)methyl]piperazin-1-yl]benzamide Chemical compound CN([C@@H](C)C=1C=CC=CC=1)C(=O)N(C)C(C(=C1)[N+]([O-])=O)=CC=C1S(=O)(=O)NC(=O)C(C=C1)=CC=C1N(CC1)CCN1CC1=CC=CC=C1C1=CC=CC=C1 URAOSMGQEFPAGH-PMERELPUSA-N 0.000 description 1
- QULHVPMNZBNJDM-UHFFFAOYSA-N n-[4-[methyl-[methyl-[4-(trifluoromethoxy)phenyl]carbamoyl]amino]-3-nitrophenyl]sulfonyl-4-[4-[(2-phenylphenyl)methyl]piperazin-1-yl]benzamide Chemical compound C=1C=C(OC(F)(F)F)C=CC=1N(C)C(=O)N(C)C(C(=C1)[N+]([O-])=O)=CC=C1S(=O)(=O)NC(=O)C(C=C1)=CC=C1N(CC1)CCN1CC1=CC=CC=C1C1=CC=CC=C1 QULHVPMNZBNJDM-UHFFFAOYSA-N 0.000 description 1
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- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
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- 210000000056 organ Anatomy 0.000 description 1
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- PLQIOFZPHAZJAM-UHFFFAOYSA-N oxo(phenyl)methanesulfonamide Chemical class NS(=O)(=O)C(=O)C1=CC=CC=C1 PLQIOFZPHAZJAM-UHFFFAOYSA-N 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 108700025694 p53 Genes Proteins 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
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- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- 230000001737 promoting effect Effects 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- YGDICLRMNDWZAK-UHFFFAOYSA-N quinolin-3-ylboronic acid Chemical compound C1=CC=CC2=CC(B(O)O)=CN=C21 YGDICLRMNDWZAK-UHFFFAOYSA-N 0.000 description 1
- KXJJSKYICDAICD-UHFFFAOYSA-N quinolin-8-ylboronic acid Chemical compound C1=CN=C2C(B(O)O)=CC=CC2=C1 KXJJSKYICDAICD-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 1
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- 229940124530 sulfonamide Drugs 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide pyridine complex Chemical compound O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
- 229960001674 tegafur Drugs 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000004360 trifluorophenyl group Chemical group 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical class [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical class [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
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- DIHAURBCYGTGCV-UHFFFAOYSA-N xi-4,5-Dihydro-2,4(5)-dimethyl-1H-imidazole Chemical compound CC1CN=C(C)N1 DIHAURBCYGTGCV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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| US51969503P | 2003-11-13 | 2003-11-13 | |
| US519695P | 2003-11-13 |
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| ES16156059T Expired - Lifetime ES2697403T3 (es) | 2003-11-13 | 2004-11-12 | Promotores de la apoptosis de N-acilsulfonamidas |
| ES04810896.3T Expired - Lifetime ES2569327T3 (es) | 2003-11-13 | 2004-11-12 | Promotores de la apoptosis que contienen N-acilsulfonamida |
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| ES16156059T Expired - Lifetime ES2697403T3 (es) | 2003-11-13 | 2004-11-12 | Promotores de la apoptosis de N-acilsulfonamidas |
| ES04810896.3T Expired - Lifetime ES2569327T3 (es) | 2003-11-13 | 2004-11-12 | Promotores de la apoptosis que contienen N-acilsulfonamida |
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| EP (3) | EP3048098B1 (pt) |
| JP (1) | JP4870570B2 (pt) |
| KR (1) | KR101157408B1 (pt) |
| CN (1) | CN1906183B (pt) |
| AU (1) | AU2004290666B2 (pt) |
| BR (1) | BRPI0416602B1 (pt) |
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| DK (2) | DK1685119T3 (pt) |
| ES (3) | ES2461615T3 (pt) |
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-
2004
- 2004-11-03 WO PCT/US2004/036770 patent/WO2005049593A2/en not_active Ceased
- 2004-11-12 PL PL10178948T patent/PL2308812T3/pl unknown
- 2004-11-12 PT PT101789485T patent/PT2308812E/pt unknown
- 2004-11-12 ES ES10178948.5T patent/ES2461615T3/es not_active Expired - Lifetime
- 2004-11-12 KR KR1020067011673A patent/KR101157408B1/ko not_active Expired - Lifetime
- 2004-11-12 NZ NZ547160A patent/NZ547160A/en not_active IP Right Cessation
- 2004-11-12 BR BRPI0416602-7A patent/BRPI0416602B1/pt not_active IP Right Cessation
- 2004-11-12 CA CA2546101A patent/CA2546101C/en not_active Expired - Lifetime
- 2004-11-12 DK DK04810896.3T patent/DK1685119T3/en active
- 2004-11-12 JP JP2006539928A patent/JP4870570B2/ja not_active Expired - Lifetime
- 2004-11-12 SI SI200432151T patent/SI2308812T1/sl unknown
- 2004-11-12 US US10/988,338 patent/US20050159427A1/en not_active Abandoned
- 2004-11-12 EP EP16156059.4A patent/EP3048098B1/en not_active Expired - Lifetime
- 2004-11-12 PL PL04810896.3T patent/PL1685119T3/pl unknown
- 2004-11-12 CN CN200480040400XA patent/CN1906183B/zh not_active Expired - Lifetime
- 2004-11-12 ES ES16156059T patent/ES2697403T3/es not_active Expired - Lifetime
- 2004-11-12 WO PCT/US2004/037911 patent/WO2005049594A1/en not_active Ceased
- 2004-11-12 EP EP10178948.5A patent/EP2308812B1/en not_active Expired - Lifetime
- 2004-11-12 TW TW093134726A patent/TWI337601B/zh not_active IP Right Cessation
- 2004-11-12 PT PT04810896T patent/PT1685119E/pt unknown
- 2004-11-12 EP EP04810896.3A patent/EP1685119B1/en not_active Expired - Lifetime
- 2004-11-12 AU AU2004290666A patent/AU2004290666B2/en not_active Expired
- 2004-11-12 DK DK10178948.5T patent/DK2308812T3/da active
- 2004-11-12 SI SI200432325A patent/SI1685119T1/sl unknown
- 2004-11-12 HU HUE04810896A patent/HUE028622T2/en unknown
- 2004-11-12 ES ES04810896.3T patent/ES2569327T3/es not_active Expired - Lifetime
-
2006
- 2006-05-11 IL IL175609A patent/IL175609A/en active IP Right Grant
- 2006-05-12 ZA ZA2006/03823A patent/ZA200603823B/en unknown
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2009
- 2009-02-23 US US12/390,945 patent/US8084607B2/en not_active Expired - Lifetime
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